EVC2 and EVC are components of a complex that localizes to the base of the cilium in a so-called EvC zone just distal to the transition zone. Mutations in the genes for EVC2 and EVC are associated with the ciliopathy Ellis van Creveld syndrome and result in an abrogated response to stimulation by Hh, making EVC2 and EVC positive regulators of Hh signaling (Blair et al, 2011; Dorn et al, 2012; Caparros-Martin et al, 2013). The EVC2:EVC complex interacts with SMO in the cilium after Hh stimulation and restricts SMO localization to the EvC zone (Dorn et al, 2012; Yang et al, 2012; Caparros-Martin et al, 2013). Disruption of the EVC2:EVC complex does not interfere with SMO ciliary localization or its activation by CSNK1A1 and ADRBK1, but prevents the Hh-dependent localization of the GLI transcription factors to the tip of the cilium and abrogates the dissociation of the GLI:SUFU complex (Dorn et al, 2012; Yang et al, 2012; Caparros-Martin et al, 2013). These events are required for the activation of the GLI transcription factors in response to ligand stimulation. Localization of the EVC2:EVC complex to the EVC zone depends on an interaction between the EVC2 W peptide (a stretch of 43 amino-acids in the C-terminal tail that is missing in a disease associated EVC2-variant), and the IQCE:EFCAB7 complex. Abrogation of this interaction causes the EVC2:EVC complex to localize along the length of the cilium and disrupts production and nuclear translocation of the full length GLI2 transcriptional activator (Pusapati et al, 2014). How the Hh signal is transmitted from the SMO:EVC2:EVC complex to downstream components is not known.